Combination Chemotherapy Compared With No Treatment Following Surgery in Treating Patients With Non-small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

A LARGE-SCALE TRIAL EVALUATING ADJUVANT CHEMOTHERAPY AFTER CURATIVE RESECTION OF NON-SMALL CELL LUNG CANCER

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002823
• Other study ID #: CDR0000065002
• Secondary ID: FRE-IALTEU-96010
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: March 26, 2013
• Start date: February 1995

Study information

• Verified date: April 2011
• Source: Gustave Roussy, Cancer Campus, Grand Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if combination chemotherapy given after surgery is more effective than surgery alone for non-small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy following surgery with that of surgery alone in treating patients who have stage I, stage II, or stage IIIA non-small cell lung cancer.

Description:

OBJECTIVES: I. Compare the impact on overall survival of adjuvant cisplatin and either a vinca alkaloid or etoposide (with or without radiotherapy) vs. no adjuvant chemotherapy in patients with completely resected stage I/II/III non-small cell lung cancer. II. Assess the frequency of treatment-related deaths and severe toxic effects. III. Describe the patterns of failure, second malignancies, and toxic effects associated with each treatment regimen.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by participating institution, type of prior surgery, and pathologic stage. Each participating center will determine which combination chemotherapy regimen and which of three cisplatin doses will be given to all patients treated at that center. The treatment group receives cisplatin combined with either vindesine, vinblastine, vinorelbine, or etoposide every 3-4 weeks for 3-4 courses, depending on the dose of cisplatin. The second group receives no adjuvant chemotherapy. Treating institutions determine prior to entering the trial which patients receive adjuvant radiotherapy: none; those with node-positive disease; those with N1 disease only; those with N2 disease only; or those eligible for a randomized radiotherapy trial. For patients in the treatment group, radiotherapy begins 3-4 weeks after the last course. Patients are followed at 6 months, then annually.

PROJECTED ACCRUAL: A maximum of 3,300 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3300
• Est. primary completion date: January 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

DISEASE CHARACTERISTICS: Histologically documented non-small cell lung cancer Any non-small cell histology eligible Pathologic stage I/II/III disease that is completely resected with microscopically clear margins within 60 days of entry (30 days preferred)

PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: Not specified Hematopoietic:

Not specified Hepatic: Not specified Renal: Not specified Other: No clear contraindication to chemotherapy No second malignancy except: Nonmelanomatous skin cancer Carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior thoracic radiotherapy Surgery: Complete resection required prior to entry

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• cisplatin

• etoposide

• vinblastine sulfate

• vindesine

• vinorelbine tartrate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Argentina	Getlac	Buenos Aires
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Peter MacCallum Cancer Institute	East Melbourne	Victoria
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Western Hospital	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	South Eastern Sydney Area Health Service	Randwick	New South Wales
Austria	AKH Vienna	Vienna
Belgium	A.Z. St. Jan	Brugge
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	AZ Zusters Van Barmhartigheid	Ronse
Belgium	Sint Elizabeth Ziekenhuis	Zottegem
Brazil	Porto Alegre Hospital	Porto Alegre	Rio Grande do Sul
Brazil	Instituto Nacional de Cancer	Rio de Janeiro
Brazil	University of Clementino Fraga	Rio De Janeiro
Brazil	Hospital A.C. Camargo	Sao Paulo
Chile	Clinica Las Nieves	Santiago
Colombia	Hospital Militar Central	Bogota
Colombia	Instituto Nacional De Cancerologia	Bogota
Czech Republic	Chest Disease Clinic, Charles University	Prague (Praha)
Egypt	National Cancer Institute of Egypt	Cairo
Former Yugoslavia	Institute for Lung Diseases	Belgrade
France	Centre Hospitalier Regional et Universitaire d'Angers	Angers
France	Centre Paul Papin	Angers
France	C.H. Armentieres	Armentieres
France	Centre Hospital General Robert Ballanger	Aulnay Sous Bois
France	C.H. Henri Mondor	Aurillac
France	Clinique Hauts De Seine Bagneux	Bagneux
France	C.H.G. Beauvais	Beauvais
France	Hopital Avicenne	Bobigny
France	C.M.C. Du Cedre	Bois Guillaume (Rouen)
France	Institut Bergonie	Bordeaux
France	Centre Regional Francois Baclesse	Caen
France	CHU de Caen	Caen
France	Centre Du Meridien	Cannes
France	Hopital Fontenoy	Chartres
France	Hopital Antoine Beclere	Clamart
France	Centre Hospitalier General	Compiegne
France	Hopital Intercommunal De Creteil	Creteil
France	Centre de Lute Contre le Cancer,Georges-Francois Leclerc	Dijon
France	Hopital D'Etampes	Etampes
France	C.H. De Grasse	Grasse
France	Centre Hospitalier de Lagny	Lagny
France	C.H.G. Du Havre-Hopital J. Monod	Le Havre
France	Centre Oscar Lambret	Lille
France	Centre Leon Berard	Lyon
France	Assistance Publique Hopitaux de Marseille Hopitaux Sud	Marseille
France	C.H. Nord Mayenne	Mayenne
France	Hopital Clinique Claude Bernard	Metz
France	Centre de Radiologie et de Traitement des Tumeurs	Meudon-La-Foret
France	Hopital Arnaud de Villeneuve	Montpellier
France	Clinique Hartmann	Neuilly sur Seine
France	Centre Antoine Lacassagne	Nice
France	Hopital Tenon	Paris
France	Hospital Saint-Joseph	Paris
France	Institut Curie - Section Medicale	Paris
France	Institut Mutualiste Montsouris	Paris
France	C.H.G. De Pau	Pau
France	Hopital Jean Bernard	Poitiers
France	CHU De Pontchaillou	Rennes
France	Centre Hospitalier de Saint-Brieuc	Saint-Brieuc
France	Centre du Rouget	Sarcelles
France	C.H. De Sens	Sens
France	Hopitaux Universitaire de Strasbourg	Strasbourg
France	C.H.G. Troyes	Troyes
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy
France	Institut Gustave Roussy	Villejuif
Greece	Athens University-Laikon General Hospital	Athens
Greece	Evangelismos Hospital	Athens
Greece	Sismanoglio Hospital	Athens
Greece	Sotiria Hospital Chest Diseases	Athens
Greece	University Hospital of Heraklion	Iraklion (Heraklion)	Crete
Greece	Metaxa's Memorial Cancer Hospital	Piraeus
Greece	University of Patras Medical School	Rio Patras
Greece	George Papanicolaou General Hospital	Thessaloniki
Israel	Kaplan Hospital	Rehovot
Israel	Tel-Aviv Medical Center	Tel-Aviv
Italy	Istituto Europeo Di Oncologia	Milano
Italy	Federico II University Medical School	Naples
Italy	Ospedale Cervello	Palermo
Italy	Ospedale Oncologico M. Ascoli	Palermo
Italy	Ospedale Civile Rimini	Rimini
Italy	Clinica Ars Medica	Rome
Italy	Ospedale San Filippo Neri	Rome
Italy	Istituto Di Clinica Chirurgica	Torino
Italy	Ospedale Molinette	Turin
Italy	Universita Degli Studi di Udine	Udine
Italy	Ospedale Di Borgo Trento	Verona
Japan	National Kinki Central Hospital	Osaka
Lithuania	Lithuanian Oncology Center	Vilnius
Macedonia, The Former Yugoslav R	Institute of Radiotherapy and Oncology	Skopje
Morocco	Institut National D'Oncologie	Rabat
Norway	University of Tromso	Tromso
Philippines	Lung Centre of the Philippines	Quezon City Diliman
Poland	Bialystok Medical School	Bialystok
Poland	Institute of Oncology	Lodz
Poland	Department of Children Hematology/Oncology University of Medicine Wroclaw	Wroclaw
Poland	K. Dluski Hospital-Medical Academy	Wroclaw
Poland	Regional Hospital for Lung Disease	Zdunowo
Portugal	Hospital Santa Maria	Lisbon (Lisboa)
Slovenia	University of Ljubljana	Ljubljana
South Africa	Groote Schuur Hospital, Cape Town	Cape Town
South Africa	Park Lane Oncology Practice	Johannesburg
South Africa	Sandton Oncology Centre	Johannesburg
Spain	Institut Catala d'Oncologia - Hospital Duran i Reynals	Barcelona
Spain	Hospital Virgen de las Nieves	Granada
Spain	Hospital Arnau Vilanova	Valencia
Sweden	Sahlgrenska University Hospital	Gothenburg (Goteborg)
Sweden	University Hospital of Linkoping	Linkoping
Sweden	Lund University Hospital	Lund
Sweden	Karolinska Hospital	Stockholm
Sweden	University Hospital - Uppsala	Uppsala
Switzerland	University Hospital	Basel
Switzerland	Ospedale San Giovanni	Bellinzona
Switzerland	Ratisches Kantons und Regionalspital	Chur
Switzerland	Hopital Cantonal Universitaire de Geneva	Geneva
Switzerland	Kantonsspital, Luzern	Luzern (Lucerne)
Switzerland	City Hospital Triemli	Zurich
Switzerland	Universitaetsspital	Zurich
Tunisia	Hopital Universitaire F. Bourguiba	Monastir
United States	Comprehensive Cancer Center at JFK Medical Center	Atlantis	Florida
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Gustave Roussy, Cancer Campus, Grand Paris

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Chile,  Colombia,  Czech Republic,  Egypt,  Former Yugoslavia,  France,  Greece,  Israel,  Italy,  Japan,  Lithuania,  Macedonia, The Former Yugoslav Republic of,  Morocco,  Norway,  Philippines,  Poland,  Portugal,  Slovenia,  South Africa,  Spain,  Sweden,  Switzerland,  Tunisia, 

References & Publications (12)

Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med — View Citation

Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant Cisplatin-based chemoth — View Citation

Bepler G, Olaussen KA, Vataire AL, Soria JC, Zheng Z, Dunant A, Pignon JP, Schell MJ, Fouret P, Pirker R, Filipits M, Brambilla E. ERCC1 and RRM1 in the international adjuvant lung trial by automated quantitative in situ analysis. Am J Pathol. 2011 Jan;17 — View Citation

Brambilla E, Dunant A, Filipits M, et al.: Prognostic and predictive role of alterations of the P53-bax-bcl2 pathway of apoptosis in the IALT (International Adjuvant Lung Cancer Trial). [Abstract] Lung Cancer 50 (Suppl 2): A-O-021, S10, 2005.

Filipits M, Pirker R, Dunant A, Lantuejoul S, Schmid K, Huynh A, Haddad V, André F, Stahel R, Pignon JP, Soria JC, Popper HH, Le Chevalier T, Brambilla E. Cell cycle regulators and outcome of adjuvant cisplatin-based chemotherapy in completely resected no — View Citation

Hotta K, Matsuo K, Kiura K, Ueoka H, Tanimoto M. Advances in our understanding of postoperative adjuvant chemotherapy in resectable non-small-cell lung cancer. Curr Opin Oncol. 2006 Mar;18(2):144-50. Review. — View Citation

Le Chevalier T: Results of the Randomized International Adjuvant Lung Cancer Trial (IALT): cisplatin-based chemotherapy (CT) vs no CT in 1867 patients (pts) with resected non-small cell lung cancer (NSCLC). [Abstract] Proceedings of the American Society o

Olaussen KA, Dunant A, Fouret P, Brambilla E, André F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, Stahel R, Sabatier L, Pignon JP, Tursz T, Le Chevalier T, Soria JC; IALT Bio Investigators. DNA repair by ERCC1 in non-small-cell lung cancer an — View Citation

Pignon JP, Tribodet H, Scagliotti GV, et al.: Lung Adjuvant Cisplatin Evaluation (LACE): a pooled analysis of five randomized clinical trials including 4,584 patients. [Abstract] J Clin Oncol 24 (Suppl 18): A-7008, 2006.

Reiman T, Lai R, Veillard AS, Paris E, Soria JC, Rosell R, Taron M, Graziano S, Kratzke R, Seymour L, Shepherd FA, Pignon JP, Sève P; LACE-Bio Group. Cross-validation study of class III beta-tubulin as a predictive marker for benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of four randomized trials. Ann Oncol. 2012 Jan;23(1):86-93. doi: 10.1093/annonc/mdr033. Epub 2011 Apr 6. — View Citation

Voortman J, Goto A, Mendiboure J, Sohn JJ, Schetter AJ, Saito M, Dunant A, Pham TC, Petrini I, Lee A, Khan MA, Hainaut P, Pignon JP, Brambilla E, Popper HH, Filipits M, Harris CC, Giaccone G. MicroRNA expression and clinical outcomes in patients treated w — View Citation

Wakelee HA, Schiller JH, Gandara DR. Current status of adjuvant chemotherapy for stage IB non-small-cell lung cancer: implications for the New Intergroup Trial. Clin Lung Cancer. 2006 Jul;8(1):18-21. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references